As for an artificial peptide which specifically binds to an inorganic material, it was reported that an iron oxide (Fe2O3)-binding peptide was obtained by S. Brown in 1992 (for example, see non-patent document 1). Since then, artificial peptides which bind to an inorganic material that had not been utilized by living organisms in nature until then have been obtained successively. In 2000, A. M. Belcher reported an artificial peptide binding to gallium arsenide (GaAs) (for example, see non-patent document 2) and an artificial peptide binding to calcium carbonate (CaCO3) (for example, seen on-patent document 2). Further, although a detailed mechanism of the reaction remains unknown, it is known that an inorganic material-binding peptide has a biomineralization ability for its target material.
Meanwhile, inorganic material-binding peptide motifs that have been found from inorganic materials utilized by living organisms in nature, for example, such as a silicon skeleton of diatom, a shell composed of calcium carbonate, human tooth or bone, are known to have a biomineralization ability for their target materials just like artificial peptides. Peptides that bind to an inorganic material are generally considered to be multifunctional peptides having a binding ability to a target material and biomineralization ability for the target material at the same time.
The present inventors have isolated by a phage display method, the artificial peptide TBP-1 (RKLPDAPGMHTW; SEQ ID NO: 2) that binds to titanium (for example, see non-patent document 3). TBP-1 has an ability to bind to silver and silicon other than titanium, but does not bind to gold, platinum, copper, chromium, iron, tin, or zinc, showing a high binding specificity. Further, TBP-1 has an ability to biomineralize silver or silica, and thus is also shown to be a multifunctional peptide (for example, see non-patent document 4).
Efforts have been made towards establishing a technology for controlling the positioning of functional particles at the nanoscale by utilizing these inorganic material-binding peptides. Researches have been made mainly on the following two methods. The first one is a method utilizing the binding specificity of an inorganic material-binding peptide, which is called “a direct patterning”, comprising the steps of modifying a substrate with plural kinds of inorganic materials, and positioning functional particles of interest two-dimensionally just on the specific region modified with an inorganic material. The second one is a method comprising the steps of patterning inorganic material-binding peptides by coupling such inorganic material-binding peptides on a molecular scaffold having a periodic structure or an orderly structure; and causing a “biomineralization” reaction of functional molecules on this scaffold, thereby controlling the positioning of the functional molecules. Both of these methods have been actively studied.
On the other hand, ferritin proteins have been known for long years as a protein which stores ‘atoms of “iron”, which is an essential metal and is toxic at the same time’ in living bodies. Ferritin or Ferritin-like proteins exist universally, in a wide range of organisms from animals and plants to bacteria, and is deeply related to the homeostasis of iron element in living bodies or in cells. Ferritin from higher eucaryotes such as human and horse forms a spherical shell structure consisting of a 24-mer, approximately 12 nm in diameter, formed from peptide chains whose molecular weight is about 20 kDa, and has an interior space of 7 to 8 nm. Ferritin stores an iron molecule in this interior space as a mass of nanoparticulate iron oxide. With regard to 24 subunits which constitute a protein spherical shell (cage), there are two types (type H and type L), and the constitution ratio of these types varies depending on organism species and tissues.
Ferritin stores an iron nanoparticle inside it under natural circumstances. However, under artificial circumstances, it has been revealed that ferritin can store the following substances in addition to iron: oxides of beryllium, gallium, manganese, phosphorus, uranium, lead, cobalt, nickel, chromium and the like; and nanoparticles of semiconductors and magnets such as cadmium selenide, zinc sulfide, iron sulfide and cadmium sulfide. Consequently, applied researches of ferritin in the fields of semiconductor-material engineering and of socialized health care have been actively performed.
Further, it is known that a dendrimer is a three-dimensional giant molecule synthesized step-by-step from a single branched-monomer unit and that the characteristic and functionality of a dendrimer can be controlled and modified easily. A dendrimer is synthesized by repeatedly adding building blocks (basic units) in the direction away from a multifunctional core (a divergence-type approach to synthesis) or in the direction towards a multifunctional core (convergence-type approach to synthesis), and on each occasion that a three-dimensional shell of building blocks is added, a dendrimer of a higher-generation is formed. It is also known that the density of functional groups on the surface increases as the dendrimer generation advances, which causes the dendrimer to have a greater control over the physical property. For example, integrating a hydrophilic group such as a carboxyl group into terminal functional groups makes the dendrimer soluble. It is also possible to design a dendrimer whose inside is hydrophobic while the molecular surface is hydrophilic. A dendrimer has a three-dimensional structure and provides a space inside for keeping a guest molecule, which allows a dendrimer to uptake poor water-soluble drugs. Further, it is known that a PAMAM (poly(amideamine)) dendrimer whose terminal functional groups are amino groups, is protonated at the terminal amino groups in response to an external environment such as pHs, which causes the whole dendrimer molecule to become positively charged and become larger in volume.
Furthermore, a star polymer is generally defined as a polymer having three or more polymer chains to be arms, which are connected at the core, the center of the arms. As the center core, a polyfunctional polyhalogenated compound or a cross-linked polymer of polyfunctional monomers is used. In addition, a star polymer with ten or more arms (a multi-arm star polymer) is produced by a method comprising the step of cross-linking polymer chains of monocarbanion with divinylbenzene by using a cross-linked structure of divinylbenzene as a core. Common methods for producing a starpolymer are a manufacturing method comprising coupling anionic living polymers by a polyfunctional coupling agent (an arm-first method); and a method comprising synthesizing a polyfunctional initiating seed in advance and extending the arms therefrom (a core-first method). A polymerization reaction of polymer chains to be arms, and a reaction to couple a plurality of such polymer chains to the core that is supposed to be the center, are performed separately in two stages.    Patent Document 1: Japanese Laid-Open Patent Application No. 2003-282509    Patent Document 2: Japanese Laid-Open Patent Application No. 2004-374093    Non-Patent Document 1: Proc. Natl. Acad. Sci. USA 89: 8651-, 1992    Non-Patent Document 2: Nature, 405: 665-, 2000    Non-Patent Document 3: Sano K., and ShibaK. “Δhexapeptide motif that electrostatically binds to the surface of titanium” J Am Chem Soc. 125, 14234-5 (2003)    Non-Patent Document 4: Langmuir, 21 (7), 3090-3095, 2005